Nigel Garrett, Asa Tapley, Aaron Hudson, Sufia Dadabhai, Bo Zhang, Nyaradzo M Mgodi, Jessica Andriesen, Azwidihwi Takalani, Leigh H Fisher, Jia Jin Kee, Craig A Magaret, Manuel Villaran, John Hural, Erica Andersen-Nissen, Guido Ferarri, Maurine D Miner, Bert Le Roux, Eduan Wilkinson, Richard Lessells, Tulio de Oliveira, Jackline Odhiambo, Parth Shah, Laura Polakowski, Margaret Yacovone, Taraz Samandari, Zvavahera Chirenje, Peter James Elyanu, Joseph Makhema, Ethel Kamuti, Harriet Nuwagaba-Biribonwoha, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Andreas Henri Diacon, Samantha Fry, Katherine Margaret Gill, Zaheer Ahmed Ebrahim Hoosain, Mina C Hosseinipour, Mubiana Inambao, Craig Innes, Steve Innes, Dishiki Kalonji, Margaret Kasaro, Priya Kassim, Noel Kayange, William Kilembe, Fatima Laher, Moelo Malahleha, Vongane Louisa Maluleke, Grace Mboya, Kirsten McHarry, Essack Mitha, Kathryn Mngadi, Pamela Mda, Tumelo Moloantoa, Cissy Kityo Mutuluuza, Nivashnee Naicker, Vimla Naicker, Anusha Nana, Annet Nanvubya, Maphoshane Nchabeleng, Walter Otieno, Elsje Louise Potgieter, Disebo Potloane, Zelda Punt, Jamil Said, Yashna Singh, Mohammed Siddique Tayob, Yacoob Vahed, Deo Ogema Wabwire, M Juliana McElrath, James G Kublin, Linda-Gail Bekker, Peter B Gilbert, Lawrence Corey, Glenda E Gray, Yunda Huang, Philip Kotze
{"title":"东非和南部非洲艾滋病毒感染者中mRNA-1273的杂交免疫与疫苗免疫：来自多中心CoVPN 3008 （Ubuntu）研究的前瞻性队列分析","authors":"Nigel Garrett, Asa Tapley, Aaron Hudson, Sufia Dadabhai, Bo Zhang, Nyaradzo M Mgodi, Jessica Andriesen, Azwidihwi Takalani, Leigh H Fisher, Jia Jin Kee, Craig A Magaret, Manuel Villaran, John Hural, Erica Andersen-Nissen, Guido Ferarri, Maurine D Miner, Bert Le Roux, Eduan Wilkinson, Richard Lessells, Tulio de Oliveira, Jackline Odhiambo, Parth Shah, Laura Polakowski, Margaret Yacovone, Taraz Samandari, Zvavahera Chirenje, Peter James Elyanu, Joseph Makhema, Ethel Kamuti, Harriet Nuwagaba-Biribonwoha, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Andreas Henri Diacon, Samantha Fry, Katherine Margaret Gill, Zaheer Ahmed Ebrahim Hoosain, Mina C Hosseinipour, Mubiana Inambao, Craig Innes, Steve Innes, Dishiki Kalonji, Margaret Kasaro, Priya Kassim, Noel Kayange, William Kilembe, Fatima Laher, Moelo Malahleha, Vongane Louisa Maluleke, Grace Mboya, Kirsten McHarry, Essack Mitha, Kathryn Mngadi, Pamela Mda, Tumelo Moloantoa, Cissy Kityo Mutuluuza, Nivashnee Naicker, Vimla Naicker, Anusha Nana, Annet Nanvubya, Maphoshane Nchabeleng, Walter Otieno, Elsje Louise Potgieter, Disebo Potloane, Zelda Punt, Jamil Said, Yashna Singh, Mohammed Siddique Tayob, Yacoob Vahed, Deo Ogema Wabwire, M Juliana McElrath, James G Kublin, Linda-Gail Bekker, Peter B Gilbert, Lawrence Corey, Glenda E Gray, Yunda Huang, Philip Kotze","doi":"10.1016/j.eclinm.2024.103054","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak.</p><p><strong>Methods: </strong>Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023.</p><p><strong>Findings: </strong>Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61-2.44) and 3.40% (95% CI 2.30-4.49) for COVID-19, and 0.048% (95% CI 0.00-0.10) and 0.32% (95% CI 0.59-0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p < 0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p = 0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350 cells/μl or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days.</p><p><strong>Interpretation: </strong>Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants.</p><p><strong>Funding: </strong>National Institute of Allergy and Infectious Diseases.</p>","PeriodicalId":11393,"journal":{"name":"EClinicalMedicine","volume":"80 ","pages":"103054"},"PeriodicalIF":9.6000,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788791/pdf/","citationCount":"0","resultStr":"{\"title\":\"Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study.\",\"authors\":\"Nigel Garrett, Asa Tapley, Aaron Hudson, Sufia Dadabhai, Bo Zhang, Nyaradzo M Mgodi, Jessica Andriesen, Azwidihwi Takalani, Leigh H Fisher, Jia Jin Kee, Craig A Magaret, Manuel Villaran, John Hural, Erica Andersen-Nissen, Guido Ferarri, Maurine D Miner, Bert Le Roux, Eduan Wilkinson, Richard Lessells, Tulio de Oliveira, Jackline Odhiambo, Parth Shah, Laura Polakowski, Margaret Yacovone, Taraz Samandari, Zvavahera Chirenje, Peter James Elyanu, Joseph Makhema, Ethel Kamuti, Harriet Nuwagaba-Biribonwoha, Sharlaa Badal-Faesen, William Brumskine, Soritha Coetzer, Rodney Dawson, Sinead Delany-Moretlwe, Andreas Henri Diacon, Samantha Fry, Katherine Margaret Gill, Zaheer Ahmed Ebrahim Hoosain, Mina C Hosseinipour, Mubiana Inambao, Craig Innes, Steve Innes, Dishiki Kalonji, Margaret Kasaro, Priya Kassim, Noel Kayange, William Kilembe, Fatima Laher, Moelo Malahleha, Vongane Louisa Maluleke, Grace Mboya, Kirsten McHarry, Essack Mitha, Kathryn Mngadi, Pamela Mda, Tumelo Moloantoa, Cissy Kityo Mutuluuza, Nivashnee Naicker, Vimla Naicker, Anusha Nana, Annet Nanvubya, Maphoshane Nchabeleng, Walter Otieno, Elsje Louise Potgieter, Disebo Potloane, Zelda Punt, Jamil Said, Yashna Singh, Mohammed Siddique Tayob, Yacoob Vahed, Deo Ogema Wabwire, M Juliana McElrath, James G Kublin, Linda-Gail Bekker, Peter B Gilbert, Lawrence Corey, Glenda E Gray, Yunda Huang, Philip Kotze\",\"doi\":\"10.1016/j.eclinm.2024.103054\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak.</p><p><strong>Methods: </strong>Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. 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引用次数: 0
摘要
背景：在低收入国家，mRNA- COVID-19疫苗的可及性有限，HIV感染者（PLWH）基本上被排除在临床试验之外，多中心CoVPN 3008 （Ubuntu）研究的A部分旨在评估mRNA-1273的安全性、混合免疫与疫苗免疫的相对有效性，以及在omicron爆发期间，非洲东部和南部PLWH中SARS-CoV-2病毒的持久性。方法：先前未接种艾滋病毒和/或与严重COVID-19相关的其他合并症的成年人在第一个月内接受一次（混合免疫）或两次（疫苗免疫）100 mcg剂量的祖先菌株mRNA-1273，具体取决于先前SARS-CoV-2感染的基线证据。在一项前瞻性队列研究设计中，我们使用协变量调整的Cox回归和反事实累积发病率方法来确定混合免疫与疫苗免疫在6个月内感染COVID-19和严重COVID-19的风险比和相对风险。正在进行的Ubuntu研究已在ClinicalTrials.gov （NCT05168813）上注册，这项工作从2021年12月到2023年3月进行。研究结果：在2021年12月至2022年9月期间，纳入了14,237名参与者，14,002名（83% PLWH， 69% SARS-CoV-2血清阳性）被纳入分析。疫苗接种是安全且耐受性良好的。常见的不良反应是注射部位疼痛或压痛（26.7%）、头痛（20.4%）和不适（20.3%）。严重的不良事件很少见（第一次接种后为0.8%，第二次接种后为1.1%），没有危及生命或致命的事件。在PLWH中，CD4中位数为635个细胞/μl， 18.5%存在HIV病毒血症。混合免疫组和疫苗免疫组COVID-19的6个月累积发病率分别为2.02%（95%可信区间[CI] 1.61-2.44）和3.40% (95% CI 2.30-4.49)，重症COVID-19的6个月累积发病率分别为0.048% （95% CI 0.00-0.10）和0.32% （95% CI 0.59-0.63）。在所有PLWH中，混合免疫组的COVID-19危险率低42%(危险比[HR] 0.58；95% ci 0.44-0.77；p解释：与使用祖先mRNA-1273疫苗的疫苗免疫相比，混合免疫与对COVID-19的更好保护有关。免疫功能低下的PLWH持续感染可能为新出现的变异提供了宿主。资助：国家过敏和传染病研究所。
Hybrid versus vaccine immunity of mRNA-1273 among people living with HIV in East and Southern Africa: a prospective cohort analysis from the multicentre CoVPN 3008 (Ubuntu) study.
Background: With limited access to mRNA COVID-19 vaccines in lower income countries, and people living with HIV (PLWH) largely excluded from clinical trials, Part A of the multicentre CoVPN 3008 (Ubuntu) study aimed to assess the safety of mRNA-1273, the relative effectiveness of hybrid versus vaccine immunity, and SARS-CoV-2 viral persistence among PLWH in East and Southern Africa during the omicron outbreak.
Methods: Previously unvaccinated adults with HIV and/or other comorbidities associated with severe COVID-19 received either one (hybrid immunity) or two (vaccine immunity) 100-mcg doses of ancestral strain mRNA-1273 in the first month, depending on baseline evidence of prior SARS-CoV-2 infection. In a prospective cohort study design, we used covariate-adjusted Cox regression and counterfactual cumulative incidence methods to determine the hazard ratio and relative risk of COVID-19 and severe COVID-19 with hybrid versus vaccine immunity within six months. The ongoing Ubuntu study is registered on ClinicalTrials.gov (NCT05168813) and this work was conducted from December 2021 to March 2023.
Findings: Between December 2021 and September 2022, 14,237 participants enrolled, and 14,002 (83% PLWH, 69% SARS-CoV-2 seropositive) were included in the analyses. Vaccinations were safe and well tolerated. Common adverse events were pain or tenderness at the injection site (26.7%), headache (20.4%), and malaise (20.3%). Severe adverse events were rare (0.8% of participants after the first and 1.1% after the second vaccination), and none were life-threatening or fatal. Among PLWH, the median CD4 count was 635 cells/μl and 18.5% had HIV viraemia. The six-month cumulative incidences in the hybrid immunity and vaccine immunity groups were 2.02% (95% confidence interval [CI] 1.61-2.44) and 3.40% (95% CI 2.30-4.49) for COVID-19, and 0.048% (95% CI 0.00-0.10) and 0.32% (95% CI 0.59-0.63) for severe COVID-19. Among all PLWH the hybrid immunity group had a 42% lower hazard rate of COVID-19 (hazard ratio [HR] 0.58; 95% CI 0.44-0.77; p < 0.001) and a 73% lower hazard rate of severe COVID-19 (HR 0.27; 95% CI 0.07-1.04; p = 0.056) than the vaccine immunity group, but this effect was not seen among PLWH with CD4 counts <350 cells/μl or HIV viraemia. Twenty PLWH had persistent SARS-CoV-2 virus at least 50 days.
Interpretation: Hybrid immunity was associated with superior protection from COVID-19 compared to vaccine immunity with the ancestral mRNA-1273 vaccine. Persistent infections among immunocompromised PLWH may provide reservoirs for emerging variants.
Funding: National Institute of Allergy and Infectious Diseases.
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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